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William R. Bishai, MD, PhD

Department Affiliations Department of Medicine Department of Pathology Molecular Microbiology Immunology (SHPH) Center for Tuberculosis Research
Rank Professor
Office Phone 410-955-3507
Lab Phone
Fax 410-614-8173
Email wbishai@jhmi.edu
SOM Address 108 Cancer Research Building II
Website

Bishai lab page

 

Students

Gyanu Lamichhane 1999 – 2004

Nicholas Be 2005 – 2011

Maia Schoonmaker 2006 – 2013

Brian Luna 2008 – 2014

Laurene Cheung 2009

Kathryn Winglee 2009 – 2015

Stefanie Krug 2014

Beth Ihms 2016

Research Interests

Area of Research

Bacterial gene regulation, pathogenesis, tuberculosis, latent infections, sigma factors.

Specific Research Interests

Transcription factors regulate bacterial adaptive response for switching between rapid growth leading to overt disease and stationary phase survival during which the host is colonized and at risk for disease. We study the role of stationary phase-specific transcription factors in diseases caused by Mycobacterium tuberculosis and Staphylococcus aureus. Latent tuberculosis is a colonization state which affects one-third of the world’s population and carries a significant risk for active TB. M. tuberculosis possesses 12 alternate RNA polymerase sigma factors several of which govern virulence and persistence in animal models and survival in vitro under stationary phase and stress conditions. We are using molecular genetic strategies including microarray analysis with recombinant bacteria to characterize the roles of these transcription factors in diseases caused by M. tuberculosis. Testing of virulence and persistence is performed locally using either the mouse or rabbit models of tuberculosis.

Additionally, clinical research on TB has been an active interest in the laboratory, and we have ongoing collaborative projects with other members of the Center for Tuberculosis Research on experimental therapeutics and diagnostics, both in Baltimore City and in several foreign settings.

Publications

Research Profile

• Agarwal N, Lamichhane G, Gupta R, Nolan S, Bishai WR. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 2009;460:98-102. PMID: 19516256.

• Agarwal N, Bishai WR, Microbiology, Subversion from the sidelines.Science. 2010 Jan 22;327(5964):417-8. PMID: 20093460.

• Gupta R, Lavollay M, Mainardi JL, Arthur M, Bishai WR, Lamichhane G. The Mycobacterium tuberculosis protein LdtMtw is a nonclassical transpeptidase require d for virulence and resistance to amoxicillin. Nat Med. 2010 Apr;16(4):466-9. PMID: 20305661.

• Lamichhane G, Freundlich JS, Ekins S, Wickramaratne N, Nolan ST, Bishai WR. Essential metabolites of Mycobacterium tuberculosis and their mimics. MBio. 2011 Feb 1;2(1):e00301-10. PMID: 21285434.

• Lee JH, Ammerman NC, Nolan S, Geiman DE, Lun S, Guo H, Bishai WR. Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis. Nat Commun. 2012 Mar 20;3:753. PMID: 22434196.

• Grosset J, Almeida D, Converse PJ, Tyagi S, Li SY, Ammerman NC, Pym AS, Wallengren K, Hafner R, Lalloo U, Swindells S, Bishai WR. Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15001-5. PMID: 22927424.

• Gupta S, Tyagi S, Almeida DV, Maiga MC, Ammerman NC, Bishai WR. Acceleration of Tuberculosis Treatment by Adjunctive Terapy with Verapamil as an Efflux Inhibitor. Am J Respir Crit Care Med. 2013 Jun 27. PMID: 23805786.

• Lun S, Guo H, Onajole OK, Pieroni M, gunosewoyo H, Chen G, Tipparaju SK, Ammerman NC, Kozikowski AP, Bishai WR. Indoleamides are active against drug-resistant Mycobacterium tuberculosis. Nat Commun. 2013 Dec 19;4:2907. PMID: 24352433.

• Nedeltchev GG, Raghunand TR, Jassal MS, Lun S, Cheng QJ, Bishai WR. Extrapulmonary dissemination of Mycobacterium bovis but not Mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis. Infect Immun. 2009;77:598-603. PMID: 19064634.

• Converse PJ, Karakousis PC, Klinkenberg LG, Kesavan AK, Ly LH, Allen SS, Grosset JH, Jain SK, Lamichhane G, Manabe YC, McMurray DN, Nuermberger EL, Bishai WR. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun. 2009;77:1230-7. PMID: 19103767.

• Conde MB, Efron A, Loredo C, De Souza GR, Graça NP, Cezar MC, Ram M, Chaudhary MA, Bishai WR, Kritski AL, Chaisson RE. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet. 2009;373:1183-9. PMID: 19345831.

• Davis SL, Be NA, Lamichhane G, Nimmagadda S, Pomper MG, Bishai WR, Jain SK. Bacterial thymidine kinase as a non-invasive imaging reporter for Mycobacterium tuberculosis in live animals. PLoS One. 2009;4:e6297. PMID: 19606217.

• Rifat D, Bishai WR, Karakousis PC. Phosphate Depletion: A Novel Trigger for Mycobacterium tuberculosis Persistence. J Infect Dis. 2009 Aug 17. PubMed PMID: 19686042.

• Davis SL, Nuermberger EL, Um P, Vidal C, Jedynak B, Pomper MG, Bishai WR, Jain SK. Monitoring response to TB drug treatment using [18F]-2-fluoro-deoxy-D-glucose positron emission tomography. Antimicrob Agents Chemother. 2009 Nov;53(11):4879-84. PMID:19738022.

• Olaleye OA, Bishai WR, Lie JO. Targeting the role of N-terminal methionine processing enzymes in Mycobacterium tuberculosis. Tuberculosis (Edinb). 2009 Dec; 89 Suppl 1:S55-9. PMID: 20006307.

• Paige C, Bishai WR. – Penitentiary pet or penthouse condo: the tuberculosis granuloma from the microbe’s point of view. Cell Microbiol. 2010 Mar; 12(3). PMID: 20039878.

• Olaleye O, Raghunand TR, Bhat S, He J, Tyagi S, Lamichhane G, Gu P, Zhou J, Zhang Y, Grosset J, Bishai WR, Liu JO. Methionine aminopeptidases from Mycobacterium tuberculosis as novel antimycobacterial targets. Chem Biol. 2010 Jan 29;17(1):86-97. PMID: 20142044.

• Zhang T, Bishai WR, Grosset J, Nuermberger EL. Rapid assessment of antibacterial activity against Mycobacterium ulcerans by using recombinant luminescent strains. Antimicrob Agents Chemother. 2010 Jul; 54(7):2806-13. PMID: 20421401.

• Zhang T, Bishai WR, Grosset J, Nuermberger EL. Rapid assessment of antibacterial activity against Mycobacterium ulcerans by using recombinant luminescent strains. Antimicrob Agents Chemother. 2010 Jul; 54(7):2806-13. PMID: 20421401.

• Burns KE, Cerda-Maira FA, Wang T, Li H, Bishai WR, Darwin KH. “Depupyltion” of prokaryotic ubiquitin-like protein from mycobacterial proteasome substrates. Mol Cell. 2010 Sep 10;39(5):821-7. PMID: 20705495.

• Jassal MS, Nedeltchev GG, Lee JH, Choi SW, Atudorei V, Sharp ZD, Deretic V, Timmins GS, Bishai WR. 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis. PLoS One. 2010 Aug27;5(8):e12451. PMID: 20805989.

• Nisa S, Blokpoel MC, Robertson BD, Tyndall JD, Lun S, Bishai WR, O’Toole R. Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery. J Antimicrob Chem. 2010 Nov;65(11):2347-58. PMID: 20810423.

• Klinkenberg LG, Lee JH, Bishai WR, Karakousis PC. The stringent response is required for full virulence of Mycobacterium tuberculosis in guinea pigs. J Infect Dis. 2010 Nov 1;202(9):1397-404. PMID: 20863231.

• Bishai JD, Bishai WR, Bishai DM. Heightened vulnerability to MDR-TB epidemics after controlling drug-susceptible TB. PLos One. 2010 Sep 22;5(9):e12843. PMID: 20877639.

• Pieroni M, Tipparaju SK, Lun S, Song Y, Sturm AW, Bishai WR, Kozikowski AP. Pyrido[1,2-a]benzimidazole-based agents active against tuberculosis (TB), multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB. ChemMedChem. 2011 Feb 7;6(2):334-42. doi: 10.1002/cmdc.201000490. Epub 2011 Jan 21.PMID: 21259445.

• Maloney E, Lun S, Stankowska D, Guo H, Rajagoapalan M, Bishai WR, Madiraju MV. Alterations in phospholipid catabolism in Mycobacterium tuberculosis lysX mutant. Front Microbiol. 2011 Feb 11;2:19.PMID: 21552395.

• Jassal MS, Nedeltchev GG, Osborne J, Bishai WR. A modified scoring system to describe gross pathology in the rabbit model of tuberculosis.BMC Microbiol. 2011 Mar 4;11:49. doi: 10.1186/1471-2180-11-49.PMID: 21375756.

• Be NA, Klinkenberg LG, Bishai WR, Karakousis PC, Jain SK. Strain-dependent CNS dissemination in guinea pigs after Mycobacterium tuberculosis aerosol challenge.Tuberculosis (Edinb). 2011 Sep;91(5):386-9. PMID: 21831713.

• Olaleye O, Raghunand TR, Bhat S, Chong C, Gu P, Zhou J, Zhang Y, Bishai WR, Liu JO. Characterization of clioquinol and analogues as novel inhibitors of methionine aminopeptidases from Mycobacterium tuberculosis.Tuberculosis (Edinb). 2011 Dec;91 Suppl 1:S61-5. PMID: 22115541.

• Be NA, Bishai WR, Jain SK. Role of Mycobacterium tuberculosis pknD in the pathogenesis of central nervous system tuberculosis.BMC Microbiol. 2012 Jan 13;12:7. PMID: 22243650.

• Harper J, Skerry C, Davis SL, Tasneen R, Weir M, Kramnik I, Bishai WR, Pomper MG, Nuermberger EL, Jain SK. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions.J Infect Dis. 2012 Feb 15;205(4):595-602. PMID: 22198962.

• Chopra S, Matsuyama K, Tran T, Malerich JP, Wan B, Franzblau SG, Lun S, Guo H, Maiga MC, Bishai WR, Madrid PB. Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis.J Antimicrob Chemother. 2012 Feb;67(2):415-21. PMID: 22052686.

• Maiga M, Agarwal N, Ammerman NC, Gupta R, Guo H, Maiga MC, Lun S, Bishai WR. Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model.PLoS One. 2012;7(2):e30749. PMID: 22319585.

• Pelly S, Bishai WR, Lamichhane G. A screen for non-coding RNA in Mycobacterium tuberculosis reveals a cAMP-responsive RNA that is expressed during infection. Gene. 2012 May 25;500(1):85-92. PMID: 22446041.

• Maiga M, Lun S, Guo H, Winglee K, Ammerman NC, Bishai WR. Risk of tuberculosis reactivation with tofacitinib (CP-690550). J Infect Dis. 2012 Jun;205(11):1705-8. PMID: 22474037.

• Skerry C, Harper J, Klunk M, Bishai WR, Jain SK. Adjunctive TNF inhibition with standard treatment enhances bacterial clearance in a murine model of necrotic TB granulomas.PLoS One. 2012;7(6):e39680. PMID: 22761866.

• Larsson C, Luna B, Ammerman NC, Maiga M, Agarwal N, Bishai WR. Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments.PLoS One. 2012;7(7):e37516. PMID: 22829866.

• Parthasarathy G, Lun S, Guo H, Ammerman NC, Geiman DE, Bishai WR. Rv2190c, an NlpC/P60 family protein, is required for full virulence of Mycobacterium tuberculosis.PLoS One. 2012;7(8):e43429. PMID: 22952680.

• Dwivedi VP, Bhattacharya D, Chatterjee S, Prasad DV, Chattopadhyay D, Van Kaer L, Bishai WR, Das G. Mycobacterium tuberculosis directs T helper 2 cell differentiation by inducing interleukin-1β production in dendritic cells. J Biol Chem. 2012 Sep 28;287(40):33656-63. PMID: 22810226.

• Kaul V, Bhattacharya D, Singh Y, Van Kaer L, Peters-Golden M, Bishai WR, Das G. An important role of prostanoid receptor EP2 in host resistance to Mycobacterium tuberculosis infection in mice. J Infect Dis. 2012 Dec 15;206(12):1816-25. PMID: 23033144.

• Erdemli SB, Gupta R, Bishai WR, Lamichhane G, Amzel LM, Bianchet MA. Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2. Structure. 2012 Dec 5;20(12):2103-15. PMID: 23103390.

• Singh Y, Kaul V, Mehra A, Chatterjee S, Tousif S, Dwivedi VP, Suar M, Kaer LV, Bishai WR, Das G. Mycobacterium tuberculosis controls miR-99b expression in infected murine dendritic cells to modulate host immunity. J Biol Chem. 2012 Dec 11. PMID: 23233675.

• Onajole Ok, Pieroni M, Tipparaju SK, Lun S, Stec J, Chen G, Gunosewoyo H, Guo H, Ammerman NC, Bishai WR, Kozikowski AP. Preliminary Structure-Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant M.tuberculosis Strains. J Med Chem. 2013 Apr 23. PMID: 23611124.

• Maiga M, Ammerman NC, Maiga MC, Tounkara A, Siddiqui S, Polis M, Murphy R, Bishai WR. Adjuvant host-directed therapy with type 3 and 5 phosphodiesterase inhibitors, but not type 4, shortens the duration of tuberculosis treatment. 2013 Aug 1;208(3):512-9. PMID: 23641020.

• Wong EB, Cohen KA, Bishai WR. Rising to the challenge: new therapies for tuberculosis. Trends Microbiol. 2013 Sep;21(9):493-501. PMID: 23764389.

• Grosset JH, Tyagi S, Almeida DV, Converse PJ, Li SY, Ammerman NC, Bishai WR, Enarson D, Trébucq A. Assessment of Clofazimine Activity in a Second-Line Regimen for Tuberculosis in Mice. Am J Respir Crit Care Med. 2013 Sep 1;188(5):608-12. PMID: 23822735.

• Lun S, Guo H, Adamson J, Cisar JS, Davis TD, Chavadi SS, Warren JD, Quadri LE, Tan DS, Bishai WR. Pharmacokinetic and in vivo Efficacy Studies of the Mycobactin Biosynthesis Inhibitor Salicyl-AMS in Mice. Antimicrob Agents Chemother. 2013 Oct;57(10):5138-40. PMID: 23856770.

• Bagci U, Foster B, Miller-Jaster K, Luna B, Bishai WR, Jonsson CB, Jain S, Mollura DJ. A computational pipeline for quantification of pulmonary infections in small animal models using serial PET-CT imaging. EJNMMI Res. 2013 Jul 23;3(1):55. PMID: 23879987.

• Seddon J, Kasprowicz V, Walker NF, Yuen HM, Sunpath H, Tezera L, Meintjes G, Wilkinson RJ, Bishai WR, Friedland JS, Elkington PT. Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis. J Infect Dis. 2013 Nov 15;208(10):1571-9. PMID: 23922364.

• Gupta S, Cohen KA, Winglee K, Maiga M, Diarra B., Bishai WR. Efflux Inhibition with Verapamil Potentiates Bedaquiline in Mycobacterium tuberculosis. Antimicrob Agents Chemothery. 2014 Jan; 58 (1):574-6. PMID: 24236454.

• Ordonez AA, Maiga M., Gupta S, Weinstein DA, Bishai W, Jain SK. Novel Adjunctive Therapies for the Treatment of Tuberculosis. Curr Mol Med. 2014;58(1):574-6. PMID: 24126586.

• Xu Z, Bagci U., Kubler, Luna B, Jain S, Bishai WR, Mollura DJ. Computer-aided detection and quantification of cavitary tuberculosis from CT Scans. Med Phys. 2013 Nov;40(11):113701. PMID: 24320475.

• Schoonmaker MK, Bishai WR, Lamichhane G. Nonclassical Transpeptidases of Mycobacterium tuberculosis Alter Cell Size, Morphology, the Cystosolic Matrix, Protein Localization, Virulence, and Resistance to β-Lactams.J Bacteriol. 2014 Apr;196(7):1394-402. PMID:24464457.

• Bhattacharya D, Dwivedi VP, Maiga M, Maiga M, Kaer LV, Bishai WR, Das G. Small molecule-directed immunotherapy against recurrent infection by Mycobacterium tuberculosis. J Biol Chem. 2014 Jun 6;289(23):16508-15. PMID:24711459.

• Maiga M, Choi SW, Atudorei V, Maiga MC, Sharp ZD, Bishai WR, Timmins GS. In Vitro and In Vivo Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase. MBio. 2014 Apr 15;5(2):e00990. PMID: 24736224.